phase 3 clinical project of pegylated recombinant human coagulation factor viii-fc fusion protein

Conditions: Severe Hemophilia A

Summary: to evaluate the prophylactic efficacy of recombinant human coagulation factor ⅷ-fc fusion protein (frsw117) for injection in patients with severe hemophilia a. to evaluate the safety of recombinant human coagulation factor ⅷ-fc fusion protein (frsw117) for injection in patients with severe hemophilia a. secondary purpose: to evaluate the efficacy of recombinant human coagulation factor ⅷ-fc fusion protein for injection (frsw117) in hemostasis and surgical hemostasis in patients with severe hemophilia a. to evaluate the pharmacokinetic (pk) characteristics of recombinant human coagulation factor ⅷ-fc fusion protein (frsw117) for injection in treated patients with severe hemophilia a. to evaluate the immunogenicity of recombinant human coagulation factor ⅷ-fc fusion protein (frsw117) for injection in treated patients with severe hemophilia a.


Eligibility criteria:
inclusion criteria： * 12≤ age ≤65 year-old men; * patients with clinically confirmed severe hemophilia a, i.e. at screening (central laboratory testing) or previous medical records confirm: fⅷ activity \< 1%； * previous documented treatment with any recombinant and/or blood-derived coagulation factor ⅷ products or cryoprecipitation products and dosed ≥150 exposure days (eds≥150) * normal prothrombin time (pt) or international normalized ratio (inr)\<1.3 * bleeding events were recorded in detail for at least 6 months prior to screening（participants in the on demand /ppx group were required to have at least 6 episodes of spontaneous bleeding within 6 months） * fully understand and know about this study and sign informed consent to participate in the clinical study voluntarily, subject and/or their guardian can cooperate with them for bleeding treatment at home, and have the ability to complete all study procedures exclusion criteria: 1. known or suspected allergy to the investigational drug or its excipients, including mouse or hamster proteins; 2. hypersensitivity or anaphylaxis after fⅷ or igg2 injection in the past; 3. fⅷ inhibitor positive (≥0.6 bu/ml) during the screening period, or have a history of fⅷ inhibitor positive in the past, or a family history of fⅷ inhibitor positive; 4. von willebrand factor (vwf) antigen test results were lower than the lower limit of normal value; 5. severe anemia at the screening stage (hemoglobin \&lt; 60 g/l); 6. platelet count during screening period \&lt; 100×109 /l; 7. abnormal liver function: .alanine aminotransferase (alt), or aspartate aminotransferase (ast) \>3 times upper limit of normal (uln); or serum total bilirubin (tbil) \>1.5x uln; 8. patients with abnormal renal function: creatinine clearance (ccr) \ 1.5x uln; 9. people with active hepatitis c, that is, hepatitis c virus (hcv) antibody positive and hcv rna positive; or anti-treponema pallidum specific antibody (tpha) positive; or positive for antibodies against the human immunodeficiency virus (hiv); 10. patients with coagulation dysfunction other than hemophilia a; 11. have a medical condition that may increase the risk of bleeding; 12. a history of drug or alcohol abuse; 13. have a known mental disorder that may affect trial compliance; 14. patients who have received transfusions of blood or blood components within 4 weeks prior to screening; 15. participants who had participated in other clinical trials within 1 month before screening; 16. use of any anticoagulant or antiplatelet drugs, off-label maximum dose of non-steroidal anti-inflammatory drugs (nsaid) within 7 days prior to screening; or patients who need to be treated with anticoagulant or antiplatelet drugs or off-label maximum doses of said during clinical trials; 17. severe cardiovascular and cerebrovascular disease or major thromboembolic events, such as stroke, myocardial infarction, unstable angina, congestive heart failure (new york heart association \[nyha\] grade ≥ iii), and severe arrhythmias (including qtc interphase \> 480 ms, corrected by fridericia formula), uncontrolled hypertension (systolic ≥ 160 mmhg or diastolic ≥100 mmhg), deep vein thrombosis, etc. 18. study patients who had used emesezumab within 6 months prior to first administration of the drug; 19. patients who had used monoclonal antibody therapy, fc fusion protein products (except frsw107 and frsw117), peg products (except frsw117), or intravenous immunoglobulin infusion within 3 months before the first administration of the investigational drug; 20. study patients who underwent major surgery within 3 months prior to initial drug administration (major surgery is defined in 6.2.3 perioperative management); 21. study patients who have used fⅷ preparation of any standard half-life (e.g., bycoch, coproch, biinidin, renjie, nol, antaine, etc.) within 3 days or 5 half-lives prior to first administration of the drug (taking the elderly); patients who have used any other extended half-life preparation fⅷ within 4 days or 5 half-lives prior to first dosing (for the elderly); 22. study patients with fever, severe active bacterial or viral infection, and allergies within 2 weeks before the first administration of the drug; 23. systemic immunomodulators (such as glucocorticoids \[\> 10 mg/ day equivalent dose of prednisone\], alpha-interferon, immunoglobulin, cyclophosphamide, cyclosporin, etc.) used within 14 days prior to the first administration of the study drug or planned during the study period were allowed to be inhaled, nasal spray, or topical corticosteroids; 24. those who had been vaccinated within 4 weeks prior to initial administration of the study drug; or who plan to be vaccinated during pk blood collection (only for subjects in the pk subgroup); 25. plan to have a child or sperm donation during the entire trial period and within 3 months after the last dose, or do not want to use effective physical contraception (such as condoms, diaphragms, iuds, etc.); 26. have other serious medical conditions that the researchers said could not benefit from them 27. subjects deemed unsuitable by other investigators.

Keywords: pharmacokinetics safety immunogenicity effectiveness